Background: Interleukin 10 (IL-10) is a cytokine which is intimately involved in the regulation of immune and inflammatory responses. Several studies have documented its essential role in preventing prolonged and exaggerated immune responses to antigens and irritants. In contrast to other inflammatory skin diseases decreased amounts of IL-10 have been detected in psoriatic skin. The role of IL-10 in psoriatic arthritis has not been studied.Objective: The safety, tolerance, immunologic effects and clinical activity of multiple doses of subcutaneous recombinant human IL-10 was evaluated in a randomized, double-blind, placebo-controlled, escalating dose trial in patients with active psoriatic arthritis. Patients received a 28 day course of daily subcutaneous IL-10 (1.0, 5.0,10.0 or 20.0 mg/kg) or placebo. Disease activity (both skin and joints and toxicity) was monitored throughout the study. Research included 1) functional assays of peripheral blood mononuclear cells; 2) cytokine expression (blood, synovium, skin); 3) activation of transcription factors specific for IL-10; 4) studies of the expression and function of tissue metalloproteinases and their inhibitors; 5) studies of lipid and bone turnover; and 6) MRI studies of synovial volume and inflammatory activity.Results. Although the study was not adequately powered to demonstrate efficacy no significant changes were observed in arthritis activity after treatment. In contrast, disease activity in the skin showed a trend towards improvement. Detailed immunological analysis of peripheral blood and involved tissues from these patients revealed modulation of endothelial activation, leukocyte recruitment and effector function. Th1 but not Th2 cytokine production was inhibited by IL-10. Moreover, suppressed synovial enhancement on magnetic resonance imaging (MRI) of affected joints and reduced avb3 integrin expression on vWF+ vessels in both synovial and skin biopsies indicated that IL-10 also modified angiogenesis in vivo. Of interest, IL-10 dramatically reduced serum cholesterol levels in all patients which is under further investigation. Lay SummaryInterleukin 10 is an anti-inflammatory protein produced by certain types of cells in the body in order to prevent prolonged and intense inflammatory reactions to irritants. In patients with psoriasis, limited amounts of IL-10 can be found in the involved skin. In this study we have administered different doses of IL-10 (or no drug-placebo) in 29 patents with psoriatic arthritis and monitored its safety and efficacy. In addition to studying its clinical effects, we also examined how IL-10 exerts its effects in humans. - Interleukin 10, psoriatic arthritis - Human Subjects